Deletions of IKZF1 and SPRED1 are associated with poor prognosis in a population-based series of pediatric B-cell precursor acute lymphoblastic leukemia diagnosed between 1992 and 2011
| Autor: | Kajsa Paulsson, Bertil Johansson, Andrea Biloglav, Anders Castor, M Behrendtz, Erik Forestier, Linda Olsson |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Adolescent Polymorphism Single Nucleotide Ikaros Transcription Factor Gene Frequency Recurrence Risk Factors Precursor B-Cell Lymphoblastic Leukemia-Lymphoma hemic and lymphatic diseases Internal medicine Humans Medicine Child Allele frequency Childhood Acute Lymphoblastic Leukemia B cell Adaptor Proteins Signal Transducing Retrospective Studies Chromosome Aberrations Hematology business.industry Infant Newborn Intracellular Signaling Peptides and Proteins Infant Membrane Proteins hemic and immune systems Retrospective cohort study Prognosis medicine.disease Lymphoma Leukemia Haematopoiesis medicine.anatomical_structure Child Preschool Cancer and Oncology Immunology Female business Gene Deletion |
| Zdroj: | Leukemia; 28(2), pp 302-310 (2014) |
| ISSN: | 1476-5551 |
| Popis: | Despite the favorable prognosis of childhood acute lymphoblastic leukemia (ALL), a substantial subset of patients relapses. Since this occurs not only in the high risk but also in the standard/intermediate groups, the presently used risk stratification is suboptimal. The underlying mechanisms for treatment failure include presence of genetic changes causing insensitivity to the therapy administered. To identify relapse-associated aberrations we performed single nucleotide polymorphism array analyses of 307 uniformly treated, consecutive pediatric ALL cases accrued 1992-2011. Recurrent aberrations of 14 genes in patients who subsequently relapsed or had induction failure were detected. Of these, deletions/uniparental isodisomies of ADD3, ATP10A, EBF1, IKZF1, PAN3, RAG1, SPRED1, and TBL1XR1 were significantly more common in B-cell precursor ALL patients who relapsed compared with those remaining in complete remission. In univariate analyses, age (10 years), WBC counts (>100 × 109/l), t(9;22)(q34;q11), MLL rearrangements, near-haploidy, and deletions of ATP10A, IKZF1, SPRED1, and the pseudoautosomal 1 regions on Xp/Yp were significantly associated with decreased 10-year event-free survival, with IKZF1 abnormalities being an independent risk factor in multivariate analysis irrespective of risk group. High age and deletions of IKZF1 and SPRED1 were also associated with poor overall survival. Thus, analyses of these genes provide clinically important information.Leukemia accepted article preview online, 4 July 2013; doi:10.1038/leu.2013.206. |
| Databáze: | OpenAIRE |
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